Work will continue on the synthesis and physiological evaluation of potential fluorinated volatile anesthetics. The major chemical contribution will be the fluorination of several halogenated carbonates, prepared during the first year. Fluorination of these halogenated carbonates will allow us to evaluate the contribution of a particular halogen to the anesthetic potency of the compound. Physiological testing of these halogen-containing fluorinated diethers will enable us to correlate our potency data with those reported for alkyl and fluorinated alkyl ether anesthetics. In this way, we hope to establish the contribution of the minus OCF2O minus moiety. During the first year two promising candidates were designed and synthesized. Larger quantities of these materials will be prepared and more detailed physiological studies conducted. Several related compounds will also be prepared in an effort to synthesize the compound with the highest anesthetic index for this given carbon-oxygen skeleton. Attempts will be made to obtain evidence leading to the elucidation of the mechanism of anesthesia for this class of compounds. We will also try to understand the relationship between anesthetic index and the conformational and electronic environments of these fluorinated diethers. These considerations should help in understanding the mechanism of action of these compounds and in designing other candidates. Preliminary carcinogenicity screening for all candidates will be continued.